INTERESTING CASE ROUNDS

1. INTERESTING CASE ROUNDS Alyssa Morris Emergency Medicine R3

2. Objectives • DDX for toxin induced seizures • DDX for toxin induced status epilepticus • Indications for pyridoxine • Review methylxanthine toxicity • Review MDAC

3. CASE • 19M took an unknown ingestion and had a seizure. • What is your quick ddx for drugs that cause seizure?

4. DDX Drug induced Seizure OTIS CAMPBELL • O- organophosphates • T- TCA • I- Isoniazid, insulin • S- sympathomimetics • C- camphor, cocaine • A- anticholinergic, amphetamines, anticholinergic, antidepressants • M- Methylxanthines • P- PCP • B- Benzow/d • E- EtOHw/d • L- Lithium, lidocaine • L- lead, lindane

5. DDx-Toxin induced Status • INH • Insulin/hypoglycemic agents • TCA • Theophylline • Wellbutrin • CO

6. Pyridoxine Indications • INH • Ethylene glycol • Gyromitra Mushrooms • Methylxanthines*

7. CASE • 19M who ingested 112 caffeine tablets (100mg/tab) who was brought in by friend for intractable nausea and vomiting • Total ingestion >11g (175mg/kg) • O/E: P=131,BP= 164/67, T= 37.6, 02= 98%, agitated, vomiting ++

8. CASE • Labs: • APAP/ASA – • CK 14 • Na 140, K 2.2, Cl 101, CO2 17, AG: 22 • Lactate 8.8 • pH 7.23 • Caffeine level 429mmol/L • ECG: Sinus tach, no dysrhythmias

9. CASE CONT • Continued to be tachy, ++ vomitting, no seizure and no dysrhythmias • Course in ED: • zofran 12mg • Maxeran 10g (still vomiting) • Stemitil 10mg (still vomiting) • MDAC • Central line to replace K+ • Zantac 50mg • Ativan 2mg IV x 2

10. CASE CONT • Labs in am • CK- 2280 • PO4 0.29 • K- 3.1 • Caffeine level 295mmol/L • Lactate 3.9 • Still vomiting and agitated

11. CAFFEINE • Methylxanthine • Similar to theophylline • Cause release of endogenous catecholamines • Stimulates B1 and B2 R • Structural analogue of Adenosine • NE and epinephrine release • Inhibit phosphodiesterase (degrades cAMP) • Effects like adrenergic stimulation

12. PHARMACOKINETICS • Routes: oral, IV, SC, IM, rectal • Oral almost 100% bioavailability • Peak concentration 30-60min • Diffuses readily into total body water and all tissues • Readily crosses BBB • Metabolized by Cytochrome P450 system • Active metabollite is theophylline

13. TOXICOKINETICS • Range of toxicity varies greatly • No definite conclusions from serum levels can be drawn • Lethal dose estimated: 150-200mg/kg or 5-10g • Death associated serum levels >80mm0l/L • Fatalities <200mmol/L • Survivial >400mmol/L OUR PT: 175mg/kg, serum 429mmol/L

14. CLINCIAL EFFECTS • Occur as a result of: • Adenosine antagonism • Release of endogenous catecholamines • Phosphodiesteraseinhibiton • Toxicity affects: • GI system • Cardiovascular system • CNS • MSK

15. GI • Nausea and protracted emesis • Severe and difficult to control despite use of multiple anti-emetics • Increase in gastric acid secretion and smooth muscle relaxation • Gastritis and esophagitis (more common with chronic use) • Transiently elevated liver enzymes

16. CARDIOVASCULAR • Tachydysrhythmias • Sinus tach • SVT • MAT • Afib • PVCs • VT • MI • Peripheral vasodilation (wide pulse pressure) • Hypertension or hypotension

17. PULMONARY • Stimulates CNS respiratory centre • Increased RR • Resp Alkalosis • Respiratory failure • Acute lung injury

18. CNS • H/A • Anxiety • Agitation • Insomnia • Tremor • Irritability • Hallucinations • Seizures*

19. MSK • Increases intracellular Ca++ • Smooth muscle relaxation • Tremor • Fasiculations • Myoclonus • Rhabdomyolysis

20. METABOLIC • HypoK • Shift into cells from B2 stimulation • HypoMg • HypoPO4 • HypoNa • Hyperglycemia • AGMA (lactate)

21. MANAGEMENT • Basics: IV, monitored bed • Labs to follow • extended electrolytes • Lactate • CK • +/- Serum caffeine level • CXR, ECGs

22. TREATMENT • MDAC* • Emesis • Zofran, maxeran • Dysrhythmias • Benzos • Esmolol • Lidocaine • Rhabdo • Fluids and monitor u/o

23. TREATMENT • Electrolytes • Replace, but careful b/c will become hyperK when shift back out of cell • Hypotension • Fluids • Not dopamine • Seizures • Benzos • Phenobarb • Pyridoxine

24. MDAC • Definition: more than 2 sequential doses of AC • In many cases, the number of doses administered is substantially greater • MDAC serves 2 purposes: • Prevent ongoing absorption of a drug that persists in the GIT • Enhance elimination by either disrupting enterohepatic recirculation or by enteroenteric recirculation

25. General Indications • GI decontamination for drug or poison ingestion associated with significant risk of toxicity, where supportive care/antidote alone is insufficient to ensure a satisfactory outcome • The toxin must be able to bind to AC • Must believe that a significant amount of agent is unabsorbed and is amenable to removal

26. AACT Position Statement • Position statement states use MDAC only for ingestions of • Carbamazepine • Dapsone • Phenobarbital • Quinine • Theophylline /Methylxanthines

27. Other Drugs • Shown to increase elimination of: • Digoxin • Phenobarbital • Carbamazepine • Phenylbutazone • Dapsone • Nadolol • Theophylline • Salicylate • Quinine • Cyclosporine • Propoxyphene • Nortriptyline • Amitriptyline

28. Contraindications • Any contraindication to single-dose activated charcoal • AC known not to adsorb • Airway protective reflexes are absent or expected to be lost and pt is not intubated • GI perf (esp caustic ingestion) • Increases severity of injury (hydrocarbons) • Endoscopy for dx/mx anticipated • Presence of ileus

29. Administration • Initial dose • 1g/kg or 10:1 ratio of ACT:toxin, whichever is > • Repeat dose • 0.25-0.5mg/kg every 1-6hrs • Procedure • Can be administered with cathartic for the 1st dose only • If pt vomits, repeat the dose • Can use oral, NG or OG route *Sxn tube before removal to reduce aspiration risk

30. SUMMARY • DDX for toxin induced seizures • OTIS CAMPBELL • Refractory seizures in toxic ingestion • Think about pyridoxine • Caffeine is a methylxanthine • Adrenergic stimulation • Can get refractory seizures • MDAC is indicated